The objective of this study is the elucidation of the mechanisms regulating salt and water balance, and in particular the salt and water retention of congestive heart failure. We have been particularly interested in the intrarenal distribution of blood flow, the relation between such changes in distribution and alterations in sodium and water excretion, and in the role of the juxtaglomerular apparatus and renin-angiotensin-aldosterone system, and ADH. In addition to defining flow distribution patterns we have been able to demonstrate efferent vascular systems and vascular tubular relationships characteristics of each region of the dog kidney by means of a unique double injection method. These studies will be extended to determine whether such characteristic relationships are found in the human kidney. To discover if such morphologic differences are associated with differences in sodium and water handling requires measurement of ionic composition deep within the kidney. Experiments with a new method, electron probe microanalysis, indicate that the elemental composition of single tubule cells may be measured in situ in frozen dried kidney sections. We plan to use this new approach to compare the content of tubule cells from normal and heart failure animals, and to explore the relations between macula densa elemental content, renin release and sodium excretion.